Complex signal processing in synthetic gene circuits using cooperative regulatory assemblies
Name
nihms-1032368.pdf
Description
Accepted version
Size
2.22 MB
Format
Adobe PDF
Checksum (MD5)
9c9bc43b9e0e64332a28dd2728ef947d
Author(s)
Bashor, Caleb J.
Patel, Nikit
Choubey, Sandeep
Beyzavi, Ali
Kondev, Jané
Collins, James J.
Khalil, Ahmad S.
Date Issued
April 2019
Journal
Science
Publisher
American Association for the Advancement of Science (AAAS)
Citation
Bashor, Caleb J. et al. "Complex signal processing in synthetic gene circuits using cooperative regulatory assemblies." Science 346, 6440 (May 2019): 593-597 © 2019 American Association for the Advancement of Science
Version
Author's final manuscript
Abstract
Eukaryotic genes are regulated by multivalent transcription factor complexes. Through cooperative self-assembly, these complexes perform nonlinear regulatory operations involved in cellular decision-making and signal processing. In this study, we apply this design principle to synthetic networks, testing whether engineered cooperative assemblies can program nonlinear gene circuit behavior in yeast. Using a model-guided approach, we show that specifying the strength and number of assembly subunits enables predictive tuning between linear and nonlinear regulatory responses for single- and multi-input circuits. We demonstrate that assemblies can be adjusted to control circuit dynamics. We harness this capability to engineer circuits that perform dynamic filtering, enabling frequency-dependent decoding in cell populations. Programmable cooperative assembly provides a versatile way to tune the nonlinearity of network connections, markedly expanding the engineerable behaviors available to synthetic circuits.
MIT Department
Massachusetts Institute of Technology. Institute for Medical Engineering & Science
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Synthetic Biology Center
Terms of Use
Creative Commons Attribution-Noncommercial-Share Alike
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1126/science.aau8287
